Compatibility, Microstructure, and Mechanical Properties of a Dimethyl-Sulfoxide-Pretreated Graphene-Modified Asphalt Binder.

The surface of graphene was pretreated with dimethyl sulfoxide to enhance its dispersion in asphalt. To investigate the compatibility, microstructure, and mechanical properties of a dimethyl-sulfoxide-pretreated graphene (DG)-modified asphalt (DG asphalt). The interaction between asphalt and DG, DG dispersion, functional groups, tensile performance, microscopic structures, and micromechanical properties of the DG asphalt were characterized. Results indicate that DG with a particle size range from 0 to 8 µm is uniformly dispersed in asphalt. The irregular distribution of DG enhances the stress transfer distance, thus improving the energy consumption and mechanical properties of the DG asphalt. The preparation process involves physical blending, which reduces the saturated hydrocarbon content and increases the chemical bond energy, ultimately enhancing mechanical properties. Additionally, the surface of the DG asphalt shows numerous smaller sized bee structures, which contribute to the hardening and smoothness of the asphalt surface. The stress is distributed uniformly across the surface of the DG asphalt, minimizing stress concentrations. Furthermore, the light components in asphalt are adsorbed by DG, forming intercalated structures that decrease the adhesion and energy dissipation when compared to base asphalt. The compressive stress within bee structures consumes more energy and enhances the anti-deformation capacity of the DG asphalt. However, at higher deformation levels, the slipping of intercalated DG decreases its anti-deformation capacity when compared to that of base asphalt. Nonetheless, the interaction between intercalated structures prevents rapid tensile failure in the DG asphalt.

Progress in polystyrene biodegradation by insect gut microbiota.

Polystyrene (PS) is frequently used in the plastics industry. However, its structural stability and difficulty to break down lead to an abundance of plastic waste in the environment, resulting in micro-nano plastics (MNPs). As MNPs are severe hazards to both human and environmental health, it is crucial to develop innovative treatment technologies to degrade plastic waste. The biodegradation of plastics by insect gut microorganisms has gained attention as it is environmentally friendly, efficient, and safe. However, our knowledge of the biodegradation of PS is still limited. This review summarizes recent research advances on PS biodegradation by gut microorganisms/enzymes from insect larvae of different species, and schematic pathways of the degradation process are discussed in depth. Additionally, the prospect of using modern biotechnology, such as genetic engineering and systems biology, to identify novel PS-degrading microbes/functional genes/enzymes and to realize new strategies for PS biodegradation is highlighted. Challenges and limitations faced by the application of genetically engineered microorganisms (GEMs) and multiomics technologies in the field of plastic pollution bioremediation are also discussed. This review encourages the further exploration of the biodegradation of PS by insect gut microbes/enzymes, offering a cutting-edge perspective to identify PS biodegradation pathways and create effective biodegradation strategies.

Continuous genetic monitoring of transient mesenchymal gene activities in distal tubule and collecting duct epithelial cells during renal fibrosis.

Epithelial cells (ECs) have been proposed to contribute to myofibroblasts or fibroblasts through epithelial-mesenchymal transition (EMT) during renal fibrosis. However, since EMT may occur dynamically, transiently, and reversibly during kidney fibrosis, conventional lineage tracing based on Cre-loxP recombination in renal ECs could hardly capture the transient EMT activity, yielding inconsistent results. Moreover, previous EMT research has primarily focused on renal proximal tubule ECs, with few reports of distal tubules and collecting ducts. Here, we generated dual recombinases-mediated genetic lineage tracing systems for continuous monitoring of transient mesenchymal gene expression in E-cadherin+ and EpCAM+ ECs of distal tubules and collecting ducts during renal fibrosis. Activation of key EMT-inducing transcription factor (EMT-TF) Zeb1 and mesenchymal markers αSMA, vimentin, and N-cadherin, were investigated following unilateral ureteral obstruction (UUO). Our data revealed that E-cadherin+ and EpCAM+ ECs did not transdifferentiate into myofibroblasts, nor transiently expressed these mesenchymal genes during renal fibrosis. In contrast, in vitro a large amount of cultured renal ECs upregulated mesenchymal genes in response to TGF-ß, a major inducer of EMT.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Revealing the degrading-possibility of methyl red by two azoreductases of Anoxybacillus sp. PDR2 based on molecular docking.

Azo dyes, as the most widely used synthetic dyes, are considered to be one of the culprits of water resources and environmental pollution. Anoxybacillus sp. PDR2 is a thermophilic bacterium with the ability to degrade azo dyes, whose genome contains two genes encoding azoreductases (named AzoPDR2-1 and AzoPDR2-2). In this study, through response surface methodology (RSM), when the initial pH, inoculation volume and Mg2+ addition amount were 7.18, 10.72% and 0.1 g/L respectively, the decolorization rate of methyl red (MR) (200 mg/L) could reach its maximum (98.8%). The metabolites after biodegradation were detected by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography mass spectrometry (LC-MS/MS), indicating that MR was successfully decomposed into 4-aminobenzoic acid and other small substrates. In homologous modeling, it was found that both azoreductases were flavin-dependent azoreductases, and belonged to the α/ß structure, using the Rossmann fold. In their docking results with the cofactor flavin mononucleotide (FMN), FMN bound to the surface of the protein dimer. Nicotinamide adenine dinucleotide (NADH) was superimposed on the plane of the pyrazine ring between FMN and the activity pocket of protein. Besides, both azoreductase complexes (azoreductase-FMN-NADH) exhibited a substrate preference for MR. Asn104 and Tyr74 played an important role in the combination of the azoreductase AzoPDR2-1 complex and the azoreductase AzoPDR2-2 complex with MR, respectively. This provided assistance for studying the mechanism of azoreductase biodegradation of azo dyes in thermophilic bacteria.

New insights into the typical nitrogen-containing heterocyclic compound-quinoline degradation and detoxification by microbial consortium: Integrated pathways, meta-transcriptomic analysis and toxicological evaluation.

As the primary source of COD in industrial wastewater, quinoline has aroused increasing attention because of its potential teratogenic, carcinogenic, and mutagenic effects in the environment. The activated sludge isolate quinoline-degrading microbial consortium (QDMC) efficiently metabolizes quinoline. However, the molecular underpinnings of the degradation mechanism of quinoline by QDMC have not been elucidated. High-throughput sequencing revealed that the dominant genera included Diaphorobacter, Bacteroidia, Moheibacter and Comamonas. Furthermore, a positive strong correlation was observed between the key bacterial communities (Diaphorobact and Bacteroidia) and quinoline degradation. According to metatranscriptomics, genes associated with quorum sensing, ABC transporters, component systems, carbohydrate, aromatic compound degradation, energy metabolism and amino metabolism showed high expression, thus improving adaptability of microbial community to quinoline stress. In addition, the mechanism of QDMC in adapting and resisting to extreme environmental conditions in line with the corresponding internal functional properties and promoting biogegradation efficiency was illustrated. Based on the identified products, QDMC effectively mineralized quinoline into low-toxicity metabolites through three major metabolic pathways, including hydroxyquinoline, 1,2,3,4-H-quinoline, 5,6,7,8-tetrahydroquinoline and 1-oxoquinoline pathways. Finally, toxicological, genotoxicity and phytotoxicity studies supported the detoxification of quinoline by the QDMC. This study provided a promising approach for the stable, environmental-friendly and efficient bioremediation applications for quinoline-containing wastewater.

Sulfur signaling pathway in cardiovascular disease.

Hydrogen sulfide (H2S) and sulfur dioxide (SO2), recognized as endogenous sulfur-containing gas signaling molecules, were the third and fourth molecules to be identified subsequent to nitric oxide and carbon monoxide (CO), and exerted diverse biological effects on the cardiovascular system. However, the exact mechanisms underlying the actions of H2S and SO2 have remained elusive until now. Recently, novel post-translational modifications known as S-sulfhydration and S-sulfenylation, induced by H2S and SO2 respectively, have been proposed. These modifications involve the chemical alteration of specific cysteine residues in target proteins through S-sulfhydration and S-sulfenylation, respectively. H2S induced S-sulfhydrylation can have a significant impact on various cellular processes such as cell survival, apoptosis, cell proliferation, metabolism, mitochondrial function, endoplasmic reticulum stress, vasodilation, anti-inflammatory response and oxidative stress in the cardiovascular system. Alternatively, S-sulfenylation caused by SO2 serves primarily to maintain vascular homeostasis. Additional research is warranted to explore the physiological function of proteins with specific cysteine sites, despite the considerable advancements in comprehending the role of H2S-induced S-sulfhydration and SO2-induced S-sulfenylation in the cardiovascular system. The primary objective of this review is to present a comprehensive examination of the function and potential mechanism of S-sulfhydration and S-sulfenylation in the cardiovascular system. Proteins that undergo S-sulfhydration and S-sulfenylation may serve as promising targets for therapeutic intervention and drug development in the cardiovascular system. This could potentially expedite the future development and utilization of drugs related to H2S and SO2.

Construction and validation of a nomogram for predicting the prognosis of patients with lymph node-positive invasive micropapillary carcinoma of the breast: based on SEER database and external validation cohort.

Background: Invasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer with high incidence of aggressive clinical behavior, lymph node metastasis (LNM) and poor prognosis. In the present study, using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed the clinicopathological characteristics and prognostic factors of IMPC with LNM, and constructed a prognostic nomogram. Methods: We retrospectively analyzed data for 487 breast IMPC patients with LNM in the SEER database from January 2010 to December 2015, and randomly divided these patients into a training cohort (70%) and an internal validation cohort (30%) for the construction and internal validation of the nomogram, respectively. In addition, 248 patients diagnosed with IMPC and LNM at the Fourth Hospital of Hebei Medical University from January 2010 to December 2019 were collected as an external validation cohort. Lasso regression, along with Cox regression, was used to screen risk factors. Further more, the discrimination, calibration, and clinical utility of the nomogram were assessed based on the consistency index (C-index), time-dependent receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA). Results: In summary, we identified six variables including molecular subtype of breast cancer, first malignant primary indicator, tumor grade, AJCC stage, radiotherapy and chemotherapy were independent prognostic factors in predicting the prognosis of IMPC patients with LNM (P < 0.05). Based on these factors, a nomogram was constructed for predicting 3- and 5-year overall survival (OS) of patients. The nomogram achieved a C-index of 0.789 (95%CI: 0.759-0.819) in the training cohort, 0.775 (95%CI: 0.731-0.819) in the internal validation cohort, and 0.788 (95%CI: 0.756-0.820) in the external validation cohort. According to the calculated patient risk score, the patients were divided into a high-risk group and a low-risk group, which showed a significant difference in the survival prognosis of the two groups (P<0.0001). The time-dependent ROC curves, calibration curves and DCA curves proved the superiority of the nomogram. Conclusions: We have successfully constructed a nomogram that could predict 3- and 5-year OS of IMPC patients with LNM and may assist clinicians in decision-making and personalized treatment planning.

Elastic stable intramedullary nail fixation versus submuscular plate fixation of pediatric femur shaft fractures in school age patients: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Studies of clinical outcomes that compare the elastic stable intramedullary nail (ESIN) with the submuscular plate (SMP) were controversial. The meta-analysis was performed to summarize existing evidence, aiming to determine whether ESIN was superior to SMP in pediatric femur shaft fractures. METHODS: Search strategies followed the recommendations of the Cochrane collaboration. Electronic searches such as PubMed, Embase, Web of Science, Cochrane were systematically searched for publications concerning ESIN and SMP from the inception date to March 2023. Two investigators independently searched, screened, and reviewed the full text of the article. Disagreements generated throughout the process were resolved by consensus, and if divergences remain, they were arbitrated by a third author. RESULTS: This study included 8 articles, comprising a total of 561 patients with a similar baseline. Compared to the SMP, the ESIN had shorter operation time (mean difference = -16.16; 95% CI = -22.83 to -9.48, P < .00001), and less intraoperative blood loss (mean difference = -53.62; 95% CI = -58.89 to -48.36, P < .00001), but had a higher incidence of implant irritation (odds ratio [OR] = 6.49; 95% CI = 3.01 to 13.98, P < .0001), lower limb malalignment (OR = 2.60; 95% CI = 1.12 to 6.04, P = .96) and overall complications(OR = 4.14; 95% CI = 2.51 to 6.84, P < .0001). And there was no significant difference in radiation time, length of hospital stay, limb length discrepancy, infection rate, delayed union rate and unplanned revised surgery rate (P > .05). CONCLUSIONS: Compared to the SMP, the ESIN offers shorter operative time, and less blood loss. However, the SMP is superior to ESINs in complication rates, especially regarding implant irritation and malalignment. Both methods could achieve excellent satisfactory functional outcomes. Thus, the SMP is an alternative choice in the pediatric femur shaft fracture.

Global risk factor analysis of myopia onset in children: A systematic review and meta-analysis.

INTRODUCTION: This work aimed to comprehensively assess the risk factors affecting myopia in children to develop more effective prevention and treatment strategies. To this end, data from database were employed to assess the relationship between the incidence of myopia and its risk factors. METHODS: We searched eight databases online in June 2022. Cohort studies were included that measured the connection between risk factors and myopia. Eligibility was not restricted by language. The Newcastle-Ottawa Scale (NOS) was used to measure the risk of bias and conducted GRADE evaluation to determine the certainty of evidence. Potential risk factors with positive or negative results were seen. Inplasy Registration: https://inplasy.com/inplasy-2022-4-0109/. RESULTS: Evidence that risk factors for myopia are mixed, comprising both positive (20) and null (17) findings. In 19 cohort studies on 3578 children, girls were more likely to develop myopia (RR: 1.28 [1.22-1.35]). Myopia can occur at any age, from early childhood to late adulthood. Children whose parents had myopia were more likely to develop myopia. Longer outdoor activities time (RR: 0.97 [0.95-0.98]) and less near-work time (RR: 1.05 [1.02-1.07]) appeared to be significantly decrease the incidence of myopia. Children with lower SE, longer AL, a lower magnitude of positive relative accommodation, worse presenting visual acuity, deeper anterior chamber, and thinner crystalline lens may be related to myopia onset. The burden of myopia in underprivileged countries is higher than in developed countries (RR: 5.28 [2.06-13.48]). The quality of evidence for the evaluated factors was moderate to low or very low. CONCLUSIONS: Genetic factors, environmental factors (such as excessive use of electronic products, and poor study habits) and lifestyle factors (such as lack of outdoor activities, poor nutrition, etc.) are the main risk factors for myopia in children. Myopia prevention strategies should be designed based on environmental factors, gender, parental myopia and eye indicators in order to explore a lifestyle that is more conducive to the eye health of children.

[Numerical Study on the Process of Human Brain Cooling Treated by Hemoperfusion Mild Hypothermia].

Mild hypothermia, as a common means of intraoperative nerve protection, has been used in clinical practice. Compared with the traditional methods such as freezing helmet and nasopharyngeal cooling, hypothermic blood perfusion is considered to be a promising treatment for mild hypothermia, but it lacks experimental and theoretical verification of its cooling effect. In this study, the commercial finite element simulation software COMSOL combined the Pennes equation with the cerebrovascular network model to construct a new simplified human brain model, which was further used to simulate the cooling process of cerebral hypothermic blood perfusion. When the hypothermic blood perfusion was 33 ℃, the human brain could enter the mild hypothermic state within 4 minutes. By comparing with helmet cooling, the feasibility and efficiency of the blood perfusion scheme were verified. By comparing with the calculation results based on Pennes equation, the rationality of the model constructed in this study were verified. This model can non-intrusively predict the changes of brain temperature during surgery, and provide a reference for the setting of treatment parameters such as blood temperature, so as to provide personalized realization of safer and more effective mild hypothermia neuro protection.

Finite Element Analysis of Cortical Bone Trajectory Screw Resistance to Pullout During Exposure to Different Cortical Layers Based on AbaqusCEA Software.

Objective: To investigate the maximum anti-pullout force and stress distribution of cortical bone trajectory (CBT) screws during screw pullout after contacting different cortical bone layers by finite element analysis (FEA) based on Abaqus software, and to provide evidence for increasing screw holding force during CBT screw implantation in clinical practice. Methods: Based on the plain CT data of lumbar spine of a healthy male volunteer who visited the Fourth People's Hospital of Guiyang in June 2022, and the standard screw parameters according to cortical bone trajectory screws. A three-dimensional model of L4 vertebral body and CBT screw was established. The diagnostic criteria of osteoporosis by quantitative CT of lumbar spine in China were set as 120 mg/cm3 low bone mass model. According to the number of contact layers between screws and cortical bone, the models were divided into group A: CBT screws produced one layer of cortical bone contact with the vertebral body (screw implantation point); group B: CBT pedicle screws produced two layers of cortical bone contact with the vertebral body (screw implantation point + pedicle inner edge); group C: CBT pedicle screws produced three layers of cortical bone contact with the vertebral body (screw implantation point + pedicle inner edge + outer edge of the vertebral body); group D: CBT pedicle screws produced four layers of cortical bone contact with the vertebral body (screw implantation point + pedicle upper wall + pedicle lateral wall + upper edge of the vertebral body); group E: CBT pedicle screws produced five layers of cortical bone contact with the vertebral body (screw implantation point + pedicle posteromedial medial wall + anterolateral wall of the pedicle + upper edge of the vertebral body + outer edge of the vertebral body). According to the reference, after the material assignment was completed, the axial pullout force experiment of screws was simulated on Abaqus CEA engineering software for five groups of finite element models established to observe the maximum axial pullout force of each group of models and the stress distribution of screws and vertebral bodies. For the comparative analysis between each group of models corresponding to the measured data, one-way analysis of variance was used. Results: The stress of cancellous bone failure in finite element model of group E was (8.6 ± 0.9), (8.4 ± 0.9), (8.1 ± 0.9), (8.3 ± 0.8), and (8.8 ± 0.7) MPa, respectively, and there was no significant difference between any group (P > 0.05); the maximum principal stress in the tail of screw was (195.1 ± 35.8), (290.9 ± 32.1), (317.3 ± 44.5), (396.3 ± 51.2), and (526.5 ± 53.1) MPa, respectively, and the stress in cortical bone destruction was (40.6 ± 3.5), (52.6 ± 4.2), (89.4 ± 4.9), (109.0 ± 8.3), and (129.4 ± 6.4) MPa, respectively, and there was significant difference between any group (P < 0.05); the maximum axial pullout force in group A-E was (1890.5 ± 45.0), (1913.4 ± 53.8), (2371.0 ± 108.3), (237.2 ± 43.0), and (119.5 ± 43.0), respectively. The increases were 2%, 16%, 5%, and 7%. There were significant differences between each group and group E (P < 0.05). Conclusion: Axial pullout force increases as the number of contact layers between CBT screws and cortical bone increases. The axial pullout force increases most when the cortical trajectory screw contacts the vertebral body with three layers of cortical bone, and reaches the maximum value when the number of contact layers reaches five layers, regardless of the screw tail stress and the maximum axial pullout force, so it is clinically desirable to make the screw contact more than three layers of cortical bone to obtain higher stability during screw implantation, improve screw stability, and increase the surgical fusion rate.

Targeting upregulation of the immunosuppressive activity of MDSCs with indirubin as a novel strategy to alleviate psoriasis.

BACKGROUND: Psoriasis is a chronic and incurable skin disorder that causes inflammation. There is an urgent clinical need for new treatments. We identified the natural compound indirubin as a potential potent agent for the treatment of psoriasis, but it's therapeutic effect and underlying mechanisms were not well understood. METHODS: Peripheral blood and skin tissues from psoriasis patients and healthy individuals were collected. Bioinformatics analysis was performed to investigate LAT1 expression and associated signal pathways in psoriasis skin lesions. A mouse model of psoriasis was established. Indirubin was administered separately or in combination with MDSCs depletion or adoptively transferred MDSCs. JPH203, rapamycin, siRNA, and NV5138 were further used to investigate the potential mechanism by which indirubin regulates MDSCs. RESULTS: Psoriasis patients had increased numbers of MDSCs in their blood and skin lesions, with high expression of Lat1. The upregulation of LAT1 expression and the arginine synthesis pathway was observed in psoriasis skin lesions. The number of MDSCs was increased, while their inhibitory effect on psoriatic T cells was decreased. Indirubin decreased Lat1 expression on the surface of MDSCs, inhibited mTOR pathway activation, upregulated Arg1 expression in MDSCs, and enhanced the immunosuppressive activity of MDSCs while inhibiting CD4+CCR6+ T cells. CONCLUSION: This study demonstrates indirubin's pharmacological and therapeutic effects, providing a basis for future clinical application in treating psoriasis.

Pseudomyopia as an independent risk factor for myopia onset: a prospective cohort study among school-aged children.

AIM: To investigate whether pseudomyopia is an independent risk factor for myopia onset based on a population-based cohort study. METHODS: Non-myopic children were recruited from schools in rural and urban settings of Shangdong province, China. Baseline examinations started in September 2020 and all participants were invited for a 6-month follow-up. Pseudomyopia was defined as spherical equivalent (SE) ≤-0.50 diopters (D) before cycloplegia and >-0.50D after cycloplegia. Myopia was defined as cycloplegic SE ≤-0.50D. RESULTS: A total of 2328 children (baseline age: 4-17 years) were included in the final analysis. During the 6-month follow-up, 21.1% (355/1680) pseudomyopic eyes developed myopia, and 3.8% (110/2879) non-myopic and non-pseudomyopic eyes developed myopia. After adjusting for multiple myopia risk factors, including baseline cycloplegic SE, near work and outdoor time, pseudomyopia was found to be an independent risk factor for myopia onset (relative risk=2.52, 95% CI 1.86 to 3.42). Additionally, pseudomyopic children with more myopic cycloplegic SE (p<0.001), smaller difference between cycloplegic and non-cycloplegic SE (DIFF, p<0.001), and higher binocular amplitude of accommodation (p<0.001) had higher risk of myopia development. CONCLUSION: This is an important longitudinal study to prove that pseudomyopia is an independent risk factor for myopia development among school-aged children.

An Adaptive Parameterized Domain Mapping Method and Its Application in Wheel-Rail Coupled Fault Diagnosis for Rail Vehicles.

The rapid development of cities in recent years has increased the operational pressure of rail vehicles, and due to the characteristics of rail vehicles, including harsh operating environment, frequent starting and braking, resulting in rails and wheels being prone to rail corrugation, polygons, flat scars and other faults. These faults are coupled in actual operation, leading to the deterioration of the wheel-rail contact relationship and causing harm to driving safety. Hence, the accurate detection of wheel-rail coupled faults will improve the safety of rail vehicles' operation. The dynamic modeling of rail vehicles is carried out to establish the character models of wheel-rail faults including rail corrugation, polygonization and flat scars to explore the coupling relationship and characteristics under variable speed conditions and to obtain the vertical acceleration of the axle box. An APDM time-frequency analysis method is proposed in this paper based on the PDMF adopting Rényi entropy as the evaluation index and employing a WOA to optimize the parameter set. The number of iterations of the WOA adopted in this paper is decreased by 26% and 23%, respectively, compared with PSO and SSA, which means that the WOA performs at faster convergence speed and with a more accurate Rényi entropy value. Additionally, TFR obtained using APDM realizes the localization and extraction of the coupled fault characteristics under rail vehicles' variable speed working conditions with higher energy concentration and stronger noise resistance corresponding to prominent ability of fault diagnosis. Finally, the effectiveness of the proposed method is verified using simulation and experimental results that prove the engineering application value of the proposed method.

Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPKα/SLC7A11/GPX4 axis in colorectal cancer.

The present study aims to investigate the mechanism of the nature compound gambogenic acid (GNA) on the apoptosis and ferroptosis in colorectal cancer (CRC). The effect of GNA on the proliferation of CRC cell lines were detected by MTT and clonogenic assay. The xenograft tumor model was established, and the inhibition effect of GNA were evaluated by observing the tumor growth. The endoplasmic reticulum (ER) of HCT116 was observed by using the ER tracker. The TargrtScan database was used to predict the miRNA binding sites. The level of miRNA with GNA treatment was explored by real-time quantitative PCR. The effect of ferroptosis were evaluated by detect the expression of reactive oxygen species (ROS), intracellular ferrous iron (Fe2+ ), malondialdehyde (MDA), glutathione (GSH), subunit solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase (GPX)4, transferrin, and ferritin by Western blot. GNA isolated from gamboge can inhibit the growth and proliferation of CRC cell lines in a concentration-dependent manner. GNA activated ER stress by upregulating miR-1291, and miR-1291 targeted the forkhead box protein A2 (FOXA2). GNA also induced ROS production and mediated the Fenton reaction by activating transferrin to increase Fe2+ , thus inducing ferroptosis. In addition, GNA could induce ferroptosis through the depletion of GSH and GPX4. Furthermore, GNA treatment regulated iron metabolism by activating AMPKα/SLC7A11/GPX4 signaling. In conclusion, GNA activated ER stress via miR-1291 and induced ferroptosis in CRC cells and might be a new inducer of ferroptosis, which can expand the efficacy of chemotherapy drugs.

Thiocyanate-degrading microflora alleviates thiocyanate stress on tomato seedlings by improving plant and rhizosphere microenvironment.

Thiocyanate in irrigation water can adversely affect plant growth and development. A previously constructed microflora with effective thiocyanate-degrading ability was used to investigate the potential of bacterial degradation for thiocyanate bioremediation. The root and aboveground part dry weight of plants inoculated with the degrading microflora increased by 66.67% and 88.45%, respectively, compared to those plants without the microflora. The supplementation of thiocyanate-degrading microflora (TDM) significantly alleviated the interference of thiocyanate in mineral nutrition metabolism. Moreover, the supplementation of TDM significantly reduced the activities of antioxidant enzymes, lipid peroxidation, and DNA damage and it protected plants from excessive thiocyanate, while the crucial antioxidant enzyme (peroxidase) decreased by 22.59%. Compared with the control without TDM supplementation, the soil sucrase content increased by 29.58%. The abundances of Methylophilus, Acinetobacter, unclassified Saccharimonadales, and Rhodanobacter changed from 19.92%, 6.63%, 0.79%, and 3.90%-13.19%, 0.27%, 3.06%, and 5.14%, respectively, with TDM supplementation. Caprolactam, 5,6-dimethyldecane, and pentadecanoic acid seem to have an effect on the structure of the microbial community in the rhizosphere soil. The above results indicated TDM supplementation can significantly reduce the toxic effects of thiocyanate on the tomato-soil microenvironment.

In situ reconstructed AgZn3 nanoparticles supported on zinc nanoplates for efficient CO2 electroreduction to tunable syngas.

Developing efficient electrocatalysts for CO2 reduction to syngas with tunable H2/CO ratios and high total faradaic efficiency is challenging. Herein, we report an effective catalyst composed of in situ reconstructed AgZn3 nanoparticles and Zn nanoplates for syngas synthesis, showing nearly 100% Faraday efficiency to syngas with a tunable H2/CO ratio from 2 : 1 to 1 : 2. Moreover, the in situ electrochemical measurements coupled with theoretical calculations disclose that the Zn site in AgZn3 nanoparticles and the hollow site between Ag and Zn in AgZn3 are the possible active sites for CO and H2 generation, respectively. This work has guiding significance for designing dual site catalysts for CO2 electroreduction to tunable syngas.

The Tian-Men-Dong decoction suppresses the tumour-infiltrating G-MDSCs via IL-1ß-mediated signalling in lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. AIM OF THE STUDY: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). MATERIALS AND METHODS: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1ß/TD + IL-1ß in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1ß-mediated apoptosis of G-MDSCs. RESULTS: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1ß-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. CONCLUSION: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1ß-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.